Antibodies constitute a critical component of the naturally acquired immunity that develops following frequent exposure to malaria. However, specific antibody titres have been reported to decline rapidly in the absence of reinfection, supporting the widely perceived notion that malaria infections fail to induce durable immunological memory responses. Currently, direct evidence for the presence or absence of immune memory to malaria is limited. In this study, we analysed the longevity of both antibody and B cell memory responses to malaria antigens among individuals who were living in an area of extremely low malaria transmission in northern Thailand, and who were known either to be malaria naïve or to have had a documented clinical attack of P. falciparum and/or P. vivax in the past 6 years. We found that exposure to malaria results in the generation of relatively avid antigen-specific antibodies and the establishment of populations of antigen-specific memory B cells in a significant proportion of malaria-exposed individuals. Both antibody and memory B cell responses to malaria antigens were stably maintained over time in the absence of reinfection. In a number of cases where antigen-specific antibodies were not detected in plasma, stable frequencies of antigen-specific memory B cells were nonetheless observed, suggesting that circulating memory B cells may be maintained independently of long-lived plasma cells. We conclude that infrequent malaria infections are capable of inducing long-lived antibody and memory B cell responses.

It is thought that both helper and effector functions of CD4+ T cells contribute to protective immunity to blood stage malaria infection. However, malaria infection does not induce long-term immunity and its mechanisms are not defined. In this study, we show that protective parasite-specific CD4+ T cells were depleted after infection with both lethal and nonlethal species of rodent Plasmodium. It is further shown that the depletion is confined to parasite-specific T cells because (a) ovalbumin (OVA)-specific CD4+ T cells are not depleted after either malaria infection or direct OVA antigen challenge, and (b) the depletion of parasite-specific T cells during infection does not kill bystander OVA-specific T cells. A significant consequence of the depletion of malaria parasite–specific CD4+ T cells is impaired immunity, demonstrated in mice that were less able to control parasitemia after depletion of transferred parasite-specific T cells. Using tumor necrosis factor (TNF)-RI knockout– and Fas-deficient mice, we demonstrate that the depletion of parasite-specific CD4+ T cells is not via TNF or Fas pathways. However, in vivo administration of anti–interferon (IFN)-γ antibody blocks depletion, suggesting that IFN-γ is involved in the process. Taken together, these data suggest that long-term immunity to malaria infection may be affected by an IFN-γ–mediated depletion of parasite-specific CD4+ T cells during infection. This study provides further insight into the nature of immunity to malaria and may have a significant impact on approaches taken to develop a malaria vaccine.

BackgroundAutoantibody to interferon-gamma (IFN-γ) has been reported to be associated with adult-onset immunodeficiency in patients from Asian countries. This study aimed to determine the prevalence of autoantibody to IFN-γ among non-HIV patients in northern Thailand who were repeatedly infected with unusual intracellular pathogens.MethodsA cross-sectional, case-control study was conducted between March 2011 and March 2012 at Chiang Mai University Hospital. 20 cases, non-HIV, aged 18–60 years, presented with at least 2 episodes of culture or histopathology proven opportunistic infections were enrolled. Controls comprised 20 HIV-infected patients and 20 healthy adults who were age- and sex-matched with cases. Enzyme-linked immunosorbent assay (ELISA) was used to detect the presence of antibody to IFN-γ.Results11 participants in each group were female. The mean ages were 48.1±6.4, 48.3±6.3, and 47.1±6.5 years among cases, HIV-infected, and healthy controls, respectively. The opportunistic infections among 20 cases included disseminated non-tuberculous mycobacterial (NTM) infection (19 patients/24 episodes), disseminated penicilliosis marneffei (12 patients/12 episodes), and non-typhoidal Salmonella bacteremia (7 patients/8 episodes). At the cutoff level of 99 percentile of controls, the prevalence of autoantibody to IFN-γ were 100%, 0%, and 0%, among cases, HIV-infected, and healthy controls, respectively (p-value <0.001). The mean concentrations of antibody to IFN-γ were 3.279±0.662 and 0.939±0.630 O.D. among cases with and without active opportunistic infection, respectively (p-value<0.001).ConclusionsIn northern Thailand, autoantibody to IFN-γ was strongly associated with adult-onset immunodeficiency. The level of antibody to IFN-γ in patients who had active opportunistic infection was relatively higher than those without active infection.

SummaryThe development of a malaria vaccine seems to be a definite possibility despite the fact that even individuals with a life time of endemic exposure do not develop sterile immunity. An effective malaria vaccine would be invaluable in preventing malaria-associated deaths in endemic areas, especially amongst children less than 5 years of age and pregnant women. This review discusses our current understanding of immunity against the asexual blood stage of malaria -the stage that is responsible for the symptoms of the disease -and approaches to the design of an asexual blood stage vaccine.Keywords: asexual blood stage, malaria, vaccine. Malaria and Plasmodium life cycleMalaria, a parasitic infection, is an important cause of mortality and morbidity in many parts of the world. Each year, an estimated 300-500 million people are affected worldwide. In reality, the true figure could be greater than three times this number. 1 Malaria kills 1-2 million people each year, mostly children under the age of 5 years and a significant number of pregnant women in sub-Saharan Africa. 2 It is a devastating infectious disease that not only affects the health system, but also slows the rate of long-term economic growth and development. The emergence of drug-resistant strains of the parasite has exacerbated the situation, and global climate change, disintegration of health services, human migration and population displacement have also contributed. 2 In recent years, there have also been more cases of malaria in travellers to endemic countries.Malaria is caused by unicellular protozoan parasites of the Plasmodium genus. 3 There are four species of malaria parasites that infect humans: P. falciparum, P. vivax, P. ovale and P. malariae. The most severe form of malaria is caused by P. falciparum. The severity of the disease depends largely on the species and strain of the infecting parasite, and the immunological status of the person who is infected.Cyclical fevers are the hallmark of malaria and typically occur shortly before or at the time of red blood cell (RBC) lysis as schizonts rupture to release new infectious merozoites (see below). This occurs every 48 h in P. vivax, P. ovale and P. falciparum, and every 72 h in P. malariae infection. Intense fever is accompanied by nausea, headaches and muscular pain, amongst other symptoms. In patients infected with P. vivax and P. ovale, relapse may recur months to years after initial infection. This is caused by re-activation of the silent liver-stage form of the parasites (hypnozoites). Renal failure, hypoglycaemia, hepatic dysfunction, severe anaemia, pulmonary oedema, convulsions and shock are complications in severe malaria. Cerebral malaria is a frequent presentation of severe P. falciparum infection and has been attributed in part to the unique ability of the parasites to alter the surface of infected RBC so that they bind to endothelial surfaces causing obstruction of cerebral blood flow. 4 Recent observations suggest that pro-inflammatory cytokines and nitric oxide induced by p...